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166 lines
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<title>09 January, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Towards Real-Time Airborne Pathogen Sensing: Electrostatic Capture and On-Chip LAMP Based Detection of Airborne Viral Pathogens</strong> -
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<div>
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Considerable loss of life, economic slowdown, and public health risk associated with the transmission of airborne respiratory pathogens was underscored by the recent COVID-19 pandemic. Airborne transmission of zoonotic diseases such as the highly pathogenic avian influenza (HPAI) and porcine reproductive and respiratory syndrome virus (PRRSV) has caused major disruptions to domestic and global food security. Current ambient air pathogen monitoring systems involves the collection of air samples from indoor settings suspected of viral contamination, followed by subsequent processing of capture samples to determine the presence and species of airborne viral matter. Nucleic acid amplification techniques are considered the gold standard for pathogen diagnostics. Currently, the necessary extraction and purification of viral RNA from air collector systems prior to sample analysis is both time consuming and performed manually. A monitoring system with separate air sampling and biochemical detection procedures is prone to delay the response to emergent viral threats. In this paper, we present a pathogen monitoring system that overcomes these limitations related to extraction and purification of viral samples and lays the groundwork for a real-time monitor for airborne viral pathogens. We demonstrate a high flow electrostatic precipitator system, that uses small collection wells as counter electrodes for pathogen collection. Integrated reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) is used for detection of captured viral matter within wells. On-chip heating of collection wells is enabled by integrated planar heaters and small volumes of reagent (30 ) directly to the collection wells. We present the design of such a system and show experimental results that demonstrate the use of this device for detection of aerosolized SARS- CoV-2 virus like particles (VLPs), a model pathogen for SARV-CoV-2.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.05.574431v1" target="_blank">Towards Real-Time Airborne Pathogen Sensing: Electrostatic Capture and On-Chip LAMP Based Detection of Airborne Viral Pathogens</a>
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</div></li>
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<li><strong>Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19</strong> -
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<div>
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Background: Cardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome in humans, but the mechanisms behind COVID-19-linked arrhythmias are unknown. This study explores the acute and long term effects of SARS-CoV-2 on the cardiac conduction system (CCS) in a hamster model of COVID-19. Methods: Radiotelemetry in conscious animals was used to non-invasively record electrocardiograms and subpleural pressures after intranasal SARS-CoV-2 infection. Cardiac cytokines, interferon-stimulated gene expression, and macrophage infiltration of the CCS, were assessed at 4 days and 4 weeks post-infection. A double-stranded RNA mimetic, polyinosinic:polycytidylic acid (PIC), was used in vivo and in vitro to activate viral pattern recognition receptors in the absence of SARS-CoV-2 infection. Results: COVID-19 induced pronounced tachypnea and severe cardiac conduction system (CCS) dysfunction, spanning from bradycardia to persistent atrioventricular block, although no viral protein expression was detected in the heart. Arrhythmias developed rapidly, partially reversed, and then redeveloped after the pulmonary infection was resolved, indicating persistent CCS injury. Increased cardiac cytokines, interferon-stimulated gene expression, and macrophage remodeling in the CCS accompanied the electrophysiological abnormalities. Interestingly, the arrhythmia phenotype was reproduced by cardiac injection of PIC in the absence of virus, indicating that innate immune activation was sufficient to drive the response. PIC also strongly induced cytokine secretion and robust interferon signaling in hearts, human iPSC-derived cardiomyocytes (hiPSC-CMs), and engineered heart tissues, accompanied by alterations in electrical and Ca2+ handling properties. Importantly, the pulmonary and cardiac effects of COVID-19 were blunted by in vivo inhibition of JAK/STAT signaling or by a mitochondrially-targeted antioxidant. Conclusions: The findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.05.574280v1" target="_blank">Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19</a>
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</div></li>
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<li><strong>GENOMIC PROFILING OF SARS-COV-2 STRAINS CIRCULATING IN SOUTH EASTERN REGION OF INDIA DURING THREE WAVES OF PANDEMIC</strong> -
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<div>
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Continuous bio-surveillance of SARS-CoV-2 is an ongoing task at local, national and global levels since the pandemic onset for understanding genetic evolution and vaccine efficacy. Present study was designed to track the emergence of new variants along the duration of three peaks of infection in the city of Puducherry, India. A total of 128 samples were subjected to Illumina deep RNA sequencing. The results showed predominance of uncommon, delta and omicron variants in first, second and third waves respectively. The most common pangolin lineage was B.1.560 and B.1.617.2. The study observed a total of 3133 common and 11 new mutations. The most common is in the Spike_D614G. A new set of mutations was observed in key viral factors such as NS16 that are implicated to be involved in immune evasion. This may have impact on enhanced disease virulence, vaccine efficiency and possible tolerance to current antivirals. This warrants further in vitro studies to understand the significance of the mutations. While the results presented would also augment the ongoing research on evolutionary and the genetic epidemiology of SARS-CoV-2, it also emphasizes the need for continuous genetic monitoring to predict the forthcoming threats due to the emergence of new or existing variants.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.06.574128v1" target="_blank">GENOMIC PROFILING OF SARS-COV-2 STRAINS CIRCULATING IN SOUTH EASTERN REGION OF INDIA DURING THREE WAVES OF PANDEMIC</a>
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</div></li>
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<li><strong>The kinetics of SARS-CoV-2 nsp7-11 polyprotein processing and impact on complexation with nsp16</strong> -
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<div>
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In severe-acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, polyproteins (pp1a/pp1ab) are processed into non-structural proteins (nsps), which largely form the replication/transcription complex (RTC). The polyprotein processing and complex formation is critical and offers potential therapeutic targets. However, the interplay of polyprotein processing and RTC-assembly are poorly understood. Here, we studied two key aspects: The influence of the pp1a terminal nsp11 on the order of polyprotein processing by viral main protease Mpro and the influence of polyprotein processing on core enzyme complex formation. We established a method based on native MS to determine rate constants k considering the structural environment. This enabled us to quantify the multi-reaction kinetics of coronavirus polyprotein processing for the first time. Our results serve as a blueprint for other multi-cleavage reactions. Further, it offers a detailed and quantifiable perspective to the dynamic reactions of SARS-CoV-2 polyprotein processing, which is required for development of novel antivirals.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.06.574466v1" target="_blank">The kinetics of SARS-CoV-2 nsp7-11 polyprotein processing and impact on complexation with nsp16</a>
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</div></li>
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<li><strong>Systemic Dosing of Virus-derived Serpin Improves Survival and Immunothrombotic Damage in Murine Colitis</strong> -
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<div>
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Inflammatory bowel disease (IBD) is potentially life-threatening, with risk of bleeding, clotting, infection, sepsis, cancer and toxic megacolon. Systemic and local immune and coagulation dysfunction increase IBD severity. Current treatments are partially effective, but there is no definitive cure. Serine protease cascades activate thrombotic, thrombolytic and complement pathways and are regulated by inhibitors, serpins. Viruses encode proteins evolved from endogenous central regulatory pathways. A purified secreted Myxomavirus-derived serpin, Serp-1, dosed as a systemic anti-inflammatory drug, has proven efficacy in vascular and inflammatory disorders. PEGylated Serp-1 protein (PEGSerp-1) has improved efficacy in lupus and SARS-CoV-2 models. We examined PEGSerp-1 treatment in a mouse Dextran Sodium Sulfate (DSS) colitis model. Prophylactic PEGSerp-1 significantly improved survival in acute severe 4-5% DSS colitis, reducing inflammation and crypt damage in acute 4-5% DSS induced colitis and when dosed as a chronic delayed treatment for recurrent 2% DSS colitis. PEGSerp-1 reduced iNOS+ M1 macrophage invasion, damage to crypt architecture and vascular inflammation with decreased uPAR, fXa, fibrinogen and complement activation. This work supports PEGSerp-1 as a tissue targeting serpin therapeutic.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.08.574715v1" target="_blank">Systemic Dosing of Virus-derived Serpin Improves Survival and Immunothrombotic Damage in Murine Colitis</a>
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</div></li>
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<li><strong>Through thick and thin: changes in creativity during the first lockdown of the Covid-19 pandemic.</strong> -
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<div>
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COVID-19 took us by surprise. We all had to face a new situation never encountered before and find new solutions to the problems it generated, either related to the disease or the lockdown’s consequences. The lockdown and pandemic crisis caused new issues and placed us in an entirely new context, changing our way of life, work time and conditions, and habits. Coping with such an unprecedented situation may have stimulated creativity. However, the situation also restricted our liberties and wellbeing and triggered health or psychological difficulties. Worrying, concerns, challenging conditions of confinement may have hampered creativity or its expression. Hence, wellbeing factors related to affective experience, living conditions, social interactions, as well as workload or available free time, may have impacted creativity during the lockdown. We carried out an online survey based on a self-administered questionnaire to examine whether the first lockdown period related to the COVID-19 pandemic (spring 2020) was associated with creativity changes and explore the role of several factors in these changes. We measured self-reported creativity changes using two approaches: changes in creative self-efficacy and creative activities and achievements. We related them to several variables estimating time availability, conditions of confinement, social interactions, and affective experience of the situation. Despite a global negative subjective experience of the situation, individuals who participated in our survey (n=380) reported that they were on average more creative during the lockdown than before and engaged in more creative activities. The converging results from self-perceived and activity-based measures showed that this positive change could be linked with more time availability, feeling more motivated or inspired, or the need to solve a problem. However, when negative changes in creativity were experienced, they were instead related to negative affective experiences, including stress and anxiety, a low mood, a feeling of pressure, or a lack of resources or opportunities. This study helps to document what happened during the first lockdown period in France regarding aspects of creativity, showing some positive outcomes of the situation despite its negative consequences, and providing cues about the key factors that stimulated or, on the contrary, blocked creativity.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/26qde/" target="_blank">Through thick and thin: changes in creativity during the first lockdown of the Covid-19 pandemic.</a>
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</div></li>
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<li><strong>“Urban Exodus” During COVID-19 in Mexico? Using Digital Data to Analyze Medium-Term Pandemic Impacts on Internal Population Movements</strong> -
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<div>
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Previous work documented a decline of internal population movements and an increase in outflows from large cities to less densely populated areas during COVID-19 in Global North countries. However, the impact of the pandemic on levels and patterns of human mobility across the rural-urban hierarchy in the Global South is yet to be established. Lack of data with temporal and spatial granularity has prevented us from assessing this research gap. Drawing on location data of Facebook users, we analyse how the intensity and patterns of long-distance movements (>100 Km) were affected during April 2020-May 2022 across different population density categories in Mexico. We find a decline of 40% in the total number of long-distance movements during April-December 2020, and a systematic decrease of outflows and inflows across the rural-urban hierarchy. Unlike in the Global North, outflows from large cities did not increase. The largest drop of outflows and inflows occurred in large cities, declining by 50%. Only specific flows increased during COVID-19, as those from large cities to certain towns, and intra-rural movements. The intensity and patterns of internal population movements across the rural-urban hierarchy have progressively returned to pre-pandemic levels during 2021 and 2022, as has occurred in Global North countries. However, the recovery has been slower in the large Mexican cities.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/e4au9/" target="_blank">“Urban Exodus” During COVID-19 in Mexico? Using Digital Data to Analyze Medium-Term Pandemic Impacts on Internal Population Movements</a>
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</div></li>
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<li><strong>What impact does the COVID-19 pandemic era have on the incidence of myocardial infarction-related fatalities in distinct age groups of male and female? A comparison study (2017–2022)</strong> -
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<div>
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Abstract: Several studies, conducted earlier during the SARS, MERS, and recent COVID-19 pandemic, have indicated that coronavirus infection, particularly COVID-19 can lead to cardiac damage. There have been recorded cases of myocarditis or cardiomyopathy linked to COVID-19 vaccines, specifically those that use mRNA technology such as BNT162b2 and mRNA-1273, primarily affecting males between the ages of 16 and 30. The prevalence and characteristics of sudden death due to myocardial infarction in various age groups of both males and females during the COVID-19 period have not been extensively examined as compared to the time before COVID-19. The aim of this study is to analyse and contrast the disparities in the average and proportion of abrupt fatalities associated with heart attacks (MI) in different age groups of males and females in the COVID-19 era and the time prior to the global outbreak. This study revealed that the maximum number of sudden deaths due to MI occurs at age 45 and above but below 60 years. The percent increase in mean sudden death due to MI in the Covid-19 period compared to the pre- COVID-19 period mean was highest in females (68.57%) of age groups 14 and above but below 18 years, while it was lowest in the males (9.51%) of the same age group. The lowest mean mortality, 38.5 (95% Conf. Interval-Mean-23.81 -53.19) due to MI during the study period was found in females in age groups 14 and above but below 18 years. The highest mean mortality was 9540.5 (95% Conf. Interval-Mean: 8551.93- 10529.07) due to MI during the study period observed in Male aged 45 and above but below 60 years. The overall percent increase in fatalities due to MI in 2022 compared to 2017 is greatest (88.46%) in females between 14 and 17 years, while the lowest is in females between 45 and 59 years (27.87%). In all age groups an increase in fatalities due to MI is seen in 2022 compared to 2017.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/42tcn/" target="_blank">What impact does the COVID-19 pandemic era have on the incidence of myocardial infarction-related fatalities in distinct age groups of male and female? A comparison study (2017–2022)</a>
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</div></li>
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<li><strong>“The best year” / “I struggled with everything”: Widening participation experiences of pandemic online learning</strong> -
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<div>
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Improving retention and graduate outcomes for students from a widening participation (WP) background is key to achieving more equitable outcomes. However, evidence suggests WP students experienced different challenges to their peers during the Covid-19 pandemic. With a focus on the pivot to online learning, we explored how WP students experienced HE during this time to understand which practices supported students’ access to education and which may have exacerbated existing inequalities. Data were collected across six focus groups from two Scottish universities (N = 23). While we found many similarities between WP students’ experiences and the broader student population, our findings also suggest coming from a position of relative disadvantage magnifies both positive and negative elements of online learning. Based on these findings, recommendations are made for pedagogical practice to enhance the experience of WP students specifically but can also be applied to the student population more generally.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/edarxiv/5bphj/" target="_blank">“The best year” / “I struggled with everything”: Widening participation experiences of pandemic online learning</a>
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<li><strong>DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets. Comparative report</strong> -
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<div>
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The COVID-19 pandemic has generated unprecedented health and far-reaching life consequences, triggering a global social and economic crisis through its protective measures aimed at safeguarding lives. This crisis compels social scientists and researchers to scrutinize the deficiencies in social and economic readiness and responses to the pandemic. The DEFEN-CE project, supported by the European Commission, delves into institutional strategies and power dynamics in social protection, policy formulation, and implementation. It sought to safeguard labour markets and workers by examining the governance of vulnerable groups in the (post) COVID-19 labor markets. Moreover, it aimed to generate research-based knowledge at EU and national levels, including candidate countries, on the role of social partners in creating and implementing protective policies vis-à-vis vulnerable groups. This report spotlights all key project findings both at the EU-level and the national level in 12 countries, embedding them to a conceptual understanding of vulnerability in general and labour-market related vulnerability in particular.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/v45ty/" target="_blank">DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets. Comparative report</a>
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</div></li>
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<li><strong>DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 LabourMarkets. EU-wide analysis of the Defence - database data</strong> -
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<div>
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The DEFEN-CE project’s Defence Database safeguards vulnerable groups in post-COVID-19 European labour markets. The research teams analysed data from EU-27 Member States, Turkey, and Serbia, including indicators covering policy, target groups, and social partners’ involvement. The analysis includes 853 policies.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/43msb/" target="_blank">DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 LabourMarkets. EU-wide analysis of the Defence - database data</a>
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<li><strong>A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models</strong> -
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<div>
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Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high endogenous levels of ACE2 but surprisingly did not support SARS-CoV-2 replication. Here we report that this resistance is mediated by a basally active cGAS-STING pathway culminating in interferon (IFN)-mediated restriction of SARS-CoV-2 replication at a post-entry step. Pharmacological inhibition of JAK1/2, depletion of the IFN-alpha; receptor and cGAS-STING pathway effectors substantially increased SARS-CoV-2 replication in these cell models. While depletion of cGAS or STING was sufficient to reduce the preexisting levels of IFN-stimulated genes (ISGs), SARS-CoV-2 infection in STING knockout cells independently induced ISG expression. Remarkably, SARS-CoV-2-induced ISG expression in STING knockout cell as well as in primary human airway cultures was limited to uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway, but not viral sensing or IFN production, in productively infected cells. Of note, SARS-CoV-2-infected primary human airway cells also displayed markedly lower levels of STING expression, raising the possibility that SARS-CoV-2 can target STING expression or preferentially infect cells that express low levels of STING. Finally, ectopic ACE2 overexpression overcame the IFN-mediated blocks, suggesting the ability of SARS-CoV-2 to overcome these possibly saturable blocks to infection. Our study highlights that in addition to viral receptors, basal activation of the cGAS-STING pathway and innate immune defenses may contribute to defining SARS-CoV-2 cellular tropism.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.07.574522v1" target="_blank">A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models</a>
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<li><strong>Spatial Morphoproteomic Features Predict Uniqueness of Immune Microarchitectures and Responses in Lymphoid Follicles</strong> -
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Multiplex imaging technologies allow the characterization of single cells in their cellular environments. Understanding the organization of single cells within their microenvironment and quantifying disease-status related biomarkers is essential for multiplex datasets. Here we proposed SNOWFLAKE, a graph neural network framework pipeline for the prediction of disease-status from combined multiplex cell expression and morphology in human B-cell follicles. We applied SNOWFLAKE to a multiplex dataset related to COVID-19 infection in humans and showed better predictive power of the SNOWFLAKE pipeline compared to other machine learning and deep learning methods. Moreover, we combined morphological features inside graph edge features to utilize attribution methods for extracting disease-relevant motifs from single-cell spatial graphs. The underlying subgraphs were further analyzed and associated with disease status across the dataset. We showed that SNOWFLAKE successfully extracted significant low dimensional embedding from subgraphs with a clear separation between disease status and helped characterize unique cellular interactions in the subgraphs. SNOWFLAKE is a generalizable pipeline for the analysis of multiplex imaging data modality by extracting disease-relevant subgraphs guided by graph-level prediction.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.05.574186v1" target="_blank">Spatial Morphoproteomic Features Predict Uniqueness of Immune Microarchitectures and Responses in Lymphoid Follicles</a>
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<li><strong>CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells and its pulmonary levels correlate with viral clearance in critical COVID-19 patients</strong> -
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<div>
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Upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients with critical coronavirus disease 2019 (COVID-19) present with life-threatening respiratory distress, pulmonary damage and cytokine storm. One unexplored hub in COVID-19 is the neuropeptide calcitonin gene-related peptide (CGRP), which is highly abundant in the airways and could converge in multiple aspects of COVID-19-related pulmonary pathophysiology. Whether CGRP affects SARS-CoV-2 infection directly remains elusive. We show that in critical COVID-19 patients, CGRP is increased in both plasma and lungs. Importantly, CGRP pulmonary levels are elevated in early SARS-CoV-2-positive patients, and restore to baseline upon subsequent viral clearance in SARS-CoV-2-negative patients. We further show that CGRP and its stable analogue SAX directly inhibit infection of bronchial Calu-3 epithelial cells with SARS-CoV-2 Omicron and Alpha variants in a dose-dependent manner. Both pre- and post-infection treatment with GRRP and/or SAX is enough to block SARS-CoV-2 productive infection of Calu3 cells. CGRP-mediated inhibition occurs via activation of the CGRP receptor and involves down-regulation of SARS-CoV-2 entry receptors at the surface of Calu-3 cells. Together, we propose that increased pulmonary CGRP mediates beneficial viral clearance in critical COVID-19 patients, by directly inhibiting SARS-CoV-2 infection. Hence, CGRP-based interventions could be harnessed for management of COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.05.574360v1" target="_blank">CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells and its pulmonary levels correlate with viral clearance in critical COVID-19 patients</a>
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<li><strong>Rapid Emergence and Evolution of SARS-CoV-2 Variants in Advanced HIV Infection</strong> -
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Previous studies have linked the evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic variants to persistent infections in people with immunocompromising conditions, but the evolutionary processes underlying these observations are incompletely understood. Here we used high-throughput, single-genome amplification and sequencing (HT-SGS) to obtain up to ~103 SARS-CoV-2 spike gene sequences in each of 184 respiratory samples from 22 people with HIV (PWH) and 25 people without HIV (PWOH). Twelve of 22 PWH had advanced HIV infection, defined by peripheral blood CD4 T cell counts (i.e., CD4 counts) <200 cells/L. In PWOH and PWH with CD4 counts [≥]200 cells/L, most single-genome spike sequences in each person matched one haplotype that predominated throughout the infection. By contrast, people with advanced HIV showed elevated intra-host spike diversity with a median of 46 haplotypes per person (IQR 14-114). Higher intra-host spike diversity immediately after COVID-19 symptom onset predicted longer SARS-CoV-2 RNA shedding among PWH, and intra-host spike diversity at this timepoint was significantly higher in people with advanced HIV than in PWOH. Composition of spike sequence populations in people with advanced HIV fluctuated rapidly over time, with founder sequences often replaced by groups of new haplotypes. These population-level changes were associated with a high total burden of intra-host mutations and positive selection at functionally important residues. In several cases, delayed emergence of detectable serum binding to spike was associated with positive selection for presumptive antibody-escape mutations. Taken together, our findings show remarkable intra-host genetic diversity of SARS-CoV-2 in advanced HIV infection and suggest that adaptive intra-host SARS-CoV-2 evolution in this setting may contribute to the emergence of new variants of concern (VOCs).
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.05.574420v1" target="_blank">Rapid Emergence and Evolution of SARS-CoV-2 Variants in Advanced HIV Infection</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Integrated Mindfulness-based Health Qigong Intervention for COVID-19 Survivors and Caregivers</strong> - <b>Conditions</b>: COVID-19 Infection <br/><b>Interventions</b>: Other: Mindfulness-based Health Qigong Intervention <br/><b>Sponsors</b>: The Hong Kong Polytechnic University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 and Influenza A/B in Point-of-Care and Non-Laboratory Settings</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Aptitude Medical Systems Metrix COVID/Flu Test <br/><b>Sponsors</b>: Aptitude Medical Systems; Biomedical Advanced Research and Development Authority <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Aerobic Exercises Versus Incentive Spirometer Device on Post-covid Pulmonary Fibrosis Patients</strong> - <b>Conditions</b>: Lung Fibrosis Interstitial; Post-COVID-19 Syndrome <br/><b>Interventions</b>: Other: Aerobic Exercises; Device: Incentive Spirometer Device; Other: Traditional Chest Physiotherapy <br/><b>Sponsors</b>: McCarious Nahad Aziz Abdelshaheed Stephens; Cairo University <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can Doctors Reduce COVID-19 Misinformation and Increase Vaccine Uptake in Ghana? A Cluster-randomised Controlled Trial</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Motivational Interviewing, AIMS; Behavioral: Facility engagement <br/><b>Sponsors</b>: London School of Economics and Political Science; Innovations for Poverty Action; Ghana Health Services <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID Ultrasound Trial</strong> - <b>Conditions</b>: Long Covid <br/><b>Interventions</b>: Device: Splenic Ultrasound <br/><b>Sponsors</b>: SecondWave Systems Inc.; University of Minnesota; MCDC (United States Department of Defense) <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity After COVID-19 Vaccines in Adapted Schedules</strong> - <b>Conditions</b>: Coronavirus Disease 2019; COVID-19 <br/><b>Interventions</b>: Drug: BNT162b2 30µg; Drug: BNT162b2 20µg; Drug: BNT162b2 6µg; Drug: mRNA-1273 100µg; Drug: mRNA-1273 50µg; Drug: ChAdOx1-S [Recombinant] <br/><b>Sponsors</b>: Universiteit Antwerpen <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Could Wearing Face Mask Have Affected Demodex Parasite</strong> - <b>Conditions</b>: Pandemic, COVID-19; Demodex Infestation <br/><b>Interventions</b>: Diagnostic Test: standard superficial skin biopsy (SSSB) <br/><b>Sponsors</b>: Nurhan Döner Aktaş <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>TDCS Stimulation After Covid-19 Infection</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Procedure: Transcranial Direct Stimulation <br/><b>Sponsors</b>: Istanbul Medipol University Hospital; Alanya Alaaddin Keykubat University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of a Booster Vaccination With an Adapted Vaccine</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Biological: PHH-1V81; Biological: Comirnaty Omicron XBB1.5 <br/><b>Sponsors</b>: Hipra Scientific, S.L.U <br/><b>Active, not recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In silico</em> Evaluation of ACE2 Inhibition by <em>Prunus armeniaca</em> L. and <em>in vivo</em> Toxicity Study</strong> - CONCLUSION: Four compounds from Prunus armeniaca seem to exert an inhibitory potential of ACE2.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Design, Synthesis, X-ray Crystallography, and Biological Activities of Covalent, Non-Peptidic Inhibitors of SARS-CoV-2 Main Protease</strong> - Highly contagious SARS-CoV-2 coronavirus has infected billions of people worldwide with flu-like symptoms since its emergence in 2019. It has caused deaths of several million people. The viral main protease (Mpro) is essential for SARS-CoV-2 replication and therefore a drug target. Several series of covalent inhibitors of Mpro were designed and synthesized. Structure-activity relationship studies show that (1) several chloroacetamide- and epoxide-based compounds targeting Cys145 are potent…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-SARS-CoV-2 Activity of a Polyphenolic Complex from Maackia amurensis</strong> - We studied the ability of the polyphenolic complex from Maackia amurensis, the active substance of Maksar, to inhibit the cytopathogenic effect induced by the SARS-CoV-2 and to reduce the concentration of viral RNA in infected Vero E6 cells. Polyphenolic complex showed significant anti-SARS-CoV-2 activity and effectively inhibited viral replication by direct action on viral particles and the early stage of viral infection.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies</strong> - Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor and plays a critical role in the immune response. TREM-1 activation leads to the production and release of proinflammatory cytokines, chemokines, as well as its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). Because patients with sepsis and septic shock show elevated sTREM-1 levels, TREM-1 has attracted attention as an important contributor to the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two Receptor Binding Strategy of SARS-CoV-2 Is Mediated by Both the N-Terminal and Receptor-Binding Spike Domain</strong> - It is not well understood why severe acute respiratory syndrome (SARS)-CoV-2 spreads much faster than other β-coronaviruses such as SARS-CoV and Middle East respiratory syndrome (MERS)-CoV. In a previous publication, we predicted the binding of the N-terminal domain (NTD) of SARS-CoV-2 spike to sialic acids (SAs). Here, we experimentally validate this interaction and present simulations that reveal a second possible interaction between SAs and the spike protein via a binding site located in the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cyclooxygenase-2/prostaglandin E2 pathway regulates infectious bronchitis virus replication in avian macrophages</strong> - Infectious bronchitis virus (IBV) is a significant respiratory pathogen that affects chickens worldwide. As an avian coronavirus, IBV leads to productive infection in chicken macrophages. However, the effects of IBV infection in macrophages on cyclooxygenase-2 (COX-2) expression are still to be elucidated. Therefore, we investigated the role of IBV infection on the production of COX-2, an enzyme involved in the synthesis of prostaglandin E2 (PGE2) in chicken macrophages. The chicken macrophage…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of natural products from virtual screenings as SARS-CoV-2 main protease inhibitors using combinational experiments</strong> - Recently, andrographolide, kaempferol, maslinic acid, rutin, and schaftoside have been identified as potent SARS-CoV-2 main protease (Mpro) inhibitors via molecular docking studies. However, no comprehensive in vitro testing of these compounds against Mpro has been conducted. In this study, we rigorously evaluated the in vitro inhibition of Mpro by these compounds using combinational experiments, including fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Chemical and spectroscopic characterization of (Artemisinin/Querctin/ Zinc) novel mixed ligand complex with assessment of its potent high antiviral activity against SARS-CoV-2 and antioxidant capacity against toxicity induced by acrylamide in male rats</strong> - A novel Artemisinin/Quercetin/Zinc (Art/Q/Zn) mixed ligand complex was synthesized, tested for its antiviral activity against coronavirus (SARS-CoV-2), and investigated for its effect against toxicity and oxidative stress induced by acrylamide (Acy), which develops upon cooking starchy foods at high temperatures. The synthesized complex was chemically characterized by performing elemental analysis, conductance measurements, FT-IR, UV, magnetic measurements, and XRD. The morphological surface of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High production <em>MBL2</em> polymorphisms protect against COVID-19 complications in critically ill patients: A retrospective cohort study</strong> - Mannose-binding lectin (MBL) binds to SARS-CoV-2, inhibits infection of susceptible cells, and activates the complement system via the lectin pathway. In this study, we investigated the association of MBL2 polymorphisms with the risk of hospitalization and clinical worsening in patients with COVID-19. A total of 550 patients with COVID-19 were included (94 non-hospitalized and 456 hospitalized). Polymorphisms in MBL2 exon 1 (codons 52, 54 and 57) and promoter region (-550, -221, and +4) were…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein</strong> - SARS-CoV-2 receptor binding domain (RBD) mediates viral entry into human cells through its interaction with angiotensin converting enzyme 2 (ACE2). Most neutralizing antibodies elicited by infection or vaccination target this domain. Such a functional relevance, together with large RBD sequence variability arising during viral spreading, point to the need of exploring the complex landscape of interactions between RBD-derived variants, ACE2 and antibodies. The current work was aimed at developing…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of an integrated sample amplification control for salivary point-of-care pathogen testing</strong> - BACKGROUND: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false-negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multifunctional polymeric guanidine and hydantoin halamines with broad biocidal activity</strong> - Prolonged and excessive use of biocides during the coronavirus disease era calls for incorporating new antiviral polymers that enhance the surface design and functionality for existing and potential future pandemics. Herein, we investigated previously unexplored polyamines with nucleophilic biguanide, guanidine, and hydantoin groups that all can be halogenated leading to high contents of oxidizing halogen that enables enhancement of the biocidal activity. Primary amino groups can be used to…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Olgotrelvir, a dual inhibitor of SARS-CoV-2 M<sup>pro</sup> and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19</strong> - CONCLUSIONS: Olgotrelvir is an oral inhibitor targeting M^(pro) and CTSL with high antiviral activity and plasma exposure and is a standalone treatment candidate for COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ligand fishing approach to explore Amaryllidaceae alkaloids as potential antiviral candidates targeting SARS-CoV-2 Nsp4</strong> - Ligand fishing, also described as affinity-based assay, represents a convenient and efficient approach to separate potential ligands from complex matrixes or chemical libraries. This approach contributes to the identification of lead compounds that can bind to a specific target. In the context of COVID-19, the search for novel therapeutic agents is crucial. Small molecule-based antiviral drugs, such as Amaryllidaceae alkaloids, have been described as potential candidates because they can inhibit…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Regulation of innate immune and inflammatory responses by supersulfides</strong> - Innate immunity plays an important role in host defense against microbial infections. It also participates in activation of acquired immunity through cytokine production and antigen presentation. Pattern recognition receptors such as Toll-like receptors and nucleotide oligomerization domain-like receptors sense invading pathogens and associated tissue injury, after which inflammatory mediators such as pro-inflammatory cytokines and nitric oxide are induced. Supersulfides are molecular species…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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